chr2-74519195-A-T

Variant names:

• chr2-74519195-A-T
• rs6546909
• NM_133637.3:c.1842T>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_133637.3(DQX1):​c.1842T>A​(p.Leu614Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,593,406 control chromosomes in the GnomAD database, including 56,858 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (14058 hom., cov: 32)
  • Exomes 𝑓: 0.19 (42800 hom.)
• Consequence: DQX1 NM_133637.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

Genes affected

DQX1 (HGNC:20410): (DEAQ-box RNA dependent ATPase 1) Predicted to enable RNA binding activity. Predicted to be involved in DNA duplex unwinding. Predicted to be part of spliceosomal complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.192 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DQX1	NM_133637.3	c.1842T>A	p.Leu614Leu	synonymous_variant	Exon 11 of 12	ENST00000404568.4	NP_598376.2
DQX1	XM_047443583.1	c.1488T>A	p.Leu496Leu	synonymous_variant	Exon 10 of 11		XP_047299539.1
DQX1	XM_011532645.1	c.1116T>A	p.Leu372Leu	synonymous_variant	Exon 8 of 9		XP_011530947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DQX1	ENST00000404568.4	c.1842T>A	p.Leu614Leu	synonymous_variant	Exon 11 of 12	5	NM_133637.3	ENSP00000384621.3
DQX1	ENST00000393951.6	c.1842T>A	p.Leu614Leu	synonymous_variant	Exon 11 of 12	2		ENSP00000377523.2
DQX1	ENST00000418139.5	n.*662T>A		non_coding_transcript_exon_variant	Exon 8 of 9	5		ENSP00000389196.1
DQX1	ENST00000418139.5	n.*662T>A		3_prime_UTR_variant	Exon 8 of 9	5		ENSP00000389196.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52112 AN: 151944 Hom.: 14018 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.299

GnomAD3 exomes AF: 0.276 AC: 65148 AN: 236390 Hom.: 14637 AF XY: 0.262 AC XY: 33577 AN XY: 128092

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.841

Gnomad SAS exome AF: 0.304

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.151

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.195 AC: 280944 AN: 1441344 Hom.: 42800 Cov.: 32 AF XY: 0.195 AC XY: 139755 AN XY: 715166

Gnomad4 AFR exome AF: 0.721

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.834

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.343 AC: 52206 AN: 152062 Hom.: 14058 Cov.: 32 AF XY: 0.343 AC XY: 25464 AN XY: 74332

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.300

Alfa AF: 0.187 Hom.: 1394

Bravo AF: 0.374

Asia WGS AF: 0.579 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.7
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6546909; hg19: chr2-74746322; COSMIC: COSV52045966; COSMIC: COSV52045966;